This Program Project (PPG) is a multidisciplinary effort dedicated to the study of Alzheimer's Disease (AD). This Project will be composed of Cores and five Individual Research Projects. A Clinical-Pathological Core will be responsible for recruiting 40 new African American and 40 new White AD patients and their families; continued longitudinal evaluations of two additional populations; the development and validation of a neuropsychological battery for patients with severe cognitive impairment; data management and analysis; arranging all autopsies; neuropathological diagnosis; and distributing and storing brain tissues. Individual Research Projects will investigate "Special Population of AD Patients" and "Synaptic Events and Their Relationship to Neuronal Death and Neuronal Plasticity." The project will continue to longitudinally assess African American and White AD caregivers and African American and White non-caregivers to determine racial differences in caregiving and to determine the effects of nursing home placement and bereavement on caregivers. The next will examine disturbances in phosphoinositide turnover in AD and control brains to characterize the specific biochemical abnormality and will examine the role of glucocorticoids in altering phosphoinositide turnover. The next project will examine a family of presynaptic proteins to determine their function in synaptogenesis and in AD. The next project will determine the role of intracellular calcium and oxidative metabolism in determining the phosphorylation state of tau. The next project utilizing a spontaneous neuronal reorganization occurring in the retrosplenial cortex, will examine the mechanisms mediating plasticity and learning deficiencies.